Postretrieval Extinction Attenuates Alcohol Cue Reactivity in Rats

Abstract

BACKGROUND Conditioned responses to alcohol-associated cues can hinder recovery from alcohol use disorder (AUD). Cue exposure (extinction) therapy (CET) can reduce reactivity to alcohol cues, but its efficacy is limited by phenomena such as spontaneous recovery and reinstatement that can cause a return of conditioned responding after extinction. Using a preclinical model of alcohol cue reactivity in rats, we evaluated whether the efficacy of alcohol CET could be improved by conducting CET during the memory reconsolidation window after retrieval of a cue-alcohol association. METHODS Rats were provided with intermittent access to unsweetened alcohol. Rats were then trained to predict alcohol access based on a visual cue. Next, rats were treated with either standard extinction (n=14) or post-retrieval extinction (n=13). Rats were then tested for long-term memory of extinction and susceptibility to spontaneous recovery and reinstatement. RESULTS Despite equivalent extinction, rats treated with post-retrieval extinction exhibited reduced spontaneous recovery and reinstatement relative to rats treated with standard extinction. CONCLUSIONS Post-retrieval CET shows promise for persistently attenuating the risk to relapse posed by alcohol cues in individuals with AUD.

Modeling Relapse to Pavlovian Alcohol‐Seeking in Rats Using Reinstatement and Spontaneous Recovery Paradigms

“…This reinstatement effect has been attributed to an excitatory context–US association that is formed during the US exposure session and summates with the residual excitatory strength of the CS that survives extinction (Bouton and Bolles, ; Bouton and Peck, ). Support for a similar process underpinning reinstatement in our paradigm comes from the observation that the volume and pattern of alcohol ingestion that occurred during the fluid exposure session produced detectable blood alcohol concentrations that correlated positively with ingested dose (experiment 4; see also Cofresi et al., ). A pharmacological effect of orally ingested alcohol may therefore have served as a US in an excitatory context–alcohol association during the fluid exposure session.…”

“…Preclinical studies show that conditioned alcohol‐seeking elicited by cues that predict alcohol can be renewed by exposure to an alcohol‐associated context following extinction in a different context (Chaudhri et al., ; Lacroix et al., ; Sciascia et al., ; Valyear et al., ). When conditioning, extinction, and test are conducted in the same context, cue‐elicited alcohol‐seeking can be reinstated by the scent of alcohol (Cofresi et al., ). These findings indicate that re‐exposure to distal and proximal environmental cues that predict alcohol can prompt a return of Pavlovian‐conditioned alcohol‐seeking after extinction.…”

Memory editing from science fiction to clinical practice

“…However, these responses are prone to relapse, suggesting that the memory of the drugcue association is inhibited but not edited by standard extinction training. By contrast, when extinction training was preceded by reactivation of the drug-cue memory, rodents showed little evidence of relapse for many drug-seeking behaviours 3,67,68 ; relapse of drug self-administration was also diminished in comparison with standard extinction, but not eliminated 3 . In human heroin and nicotine addicts, self-reported craving was reduced for up to 180 days following the retrieval-extinction procedure 3,69 , but although the nicotine addicts smoked fewer cigarettes one month later, their likelihood of relapse did not change 69 .…”

Modulation of naturalistic maladaptive memories using behavioural and pharmacological reconsolidation-interfering strategies: A systematic review and meta-analysis of clinical and 'sub-clinical' studies

“…Similarly, relative to extinction without prior retrieval, retrieval-extinction leads to enduring reductions in reactivity to drug cues in rats (e.g. Cofresí et al, 2017;Xue et al, 2012) and humans (Germeroth et al, 2017;Xue et al, 2012;see Kredlow, Unger, & Otto (2016) for a review of post-retrieval extinction effects), suggesting it is a general-purpose strategy for enduring modification of maladaptive memories. Other therapeutically applicable post-retrieval learning strategies might also be suited to updating appetitive and threat memories in humans, although these have received less attention (cf.…”